Synthesis and structure-activity relationship of non-peptidic antagonists of neuropilin-1 receptor

被引：28

作者：

Liu, Wang-Qing ^{[1
]}

Megale, A. Valentino ^{[2
]}

Borriello, Lucia ^{[1
,2
,3
]}

Leforban, Bertrand ^{[1
,3
]}

Montes, Matthieu ^{[4
]}

Goldwaser, Elodie ^{[2
,3
]}

Gresh, Nohad ^{[1
,2
]}

Piquemal, Jean-Philip ^{[5
]}

Hadj-Slimane, Reda ^{[3
]}

Hermine, Olivier ^{[6
,7
,8
]}

Garbay, Christiane ^{[1
,2
]}

Raynaud, Francoise ^{[1
,2
]}

Lepelletier, Yves ^{[6
,7
,8
]}

Demange, Luc ^{[1
,2
,9
]}

机构：

[1] Univ Paris 05, Lab Mol & Cellular Pharmacochem, INSERM U648, Sorbonne Paris Cite,UFR Biomed St Peres, F-75270 Paris 06, France

[2] Univ Paris 05, Lab Chim & Biochim Pharmacol & Toxicol, UMR CNRS 8601, Sorbonne Paris Cite,UFR Biomed St Peres, F-75270 Paris 06, France

[3] Tragex Pharma, F-92100 Boulogne, France

[4] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, Lab Genom Bioinformat & Applicat, EA 4627, F-75003 Paris, France

[5] Univ Paris 06, Sorbonne Univ, Chim Theor Lab, F-75252 Paris, France

[6] INSERM UMR 1163, Lab Cellular & Mol Basis Normal Hematopoiesis & H, F-75015 Paris, France

[7] Paris Descartes Univ, Imagine Inst, Sorbonne Paris Cite, F-75015 Paris, France

[8] CNRS ERL 8254, F-75015 Paris, France

[9] Univ Nice Sophia Antipolis, CNRS, UMR 7272, Inst Chim Nice, F-06108 Nice 1, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 17期

关键词：

Angiogenesis; Neuropilin; Protein-protein interaction; Docking to receptor; Heterocycles; ENDOTHELIAL GROWTH-FACTOR; END-RULE PEPTIDES; EFFICIENT SYNTHESIS; SEMAPHORIN-III; BREAST-CANCER; BINDING; ANGIOGENESIS; VEGF; OSTEOARTHRITIS; CORECEPTORS;

D O I：

10.1016/j.bmcl.2014.07.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Neuropilins (NRPs) are VEGF-A(165) co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A(165)/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A(165)/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4254 / 4259

页数：6

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